Melasma is an acquired, symmetric, irregular hypermelanosis on sun-exposed areas of the face, commonly seen in Latin American women, particularly those with IV-V skin types (Javaheri S M, Handa S, Kaur I et al. Safety and efficacy of glycolic acid facial peel in Indian Women with melasma. Int J Dermatol., 2001; 40:354-357).
It is a very frequent disease, although its true incidence is unknown. Many factors have been implicated in the pathogenesis of melasma; however, the most important ones remain UV radiations, hereditary predisposition, and hormonal dysfunction (Mosher D B, Fitzpatrick T B, Ortonne J-P, Hori Y. Hypomelanoses and Hypermelanoses. In: Freedberg I M, Eisen A Z, Wolff K, et al, eds. Fitzpatrick's Dermatology in General Medicine, Vol. 1. New York, N.Y.: McGraw-Hill; 1999: 945-1017; Barankin B, Silver S G, Carruthera A. The skin in pregnancy. J Cut Med Surg., 2002; 6(3): 236-40).
Melasma has historically been difficult to treat and therapy remains a challenge for this chronic condition.
The principal rules of therapy must encompass: sun protection, inhibition of tyrosinase activity, removal of melanin, and destruction or disruption of melanin granules. Pandya and Guevara particularly recommend that patients should use sunscreens to protect the skin from UV-A and UV-B radiation and also from visible light to avoid formation of new melanin and immediate darkening of preformed melanin. Those who routinely use a sunscreen along with other treatment modalities do better than those who do not (Pandya A G et al. Disorders of hyperpigmentation. Dermatol Clin., 2000; 18(1):91-98; Vasquez M. Sanchez J L, The efficacy of a broad spectrum in the treatment of melasma Cutis., 193; 32:92-96).
Topical treatments are the mainstay (Mosher D B et al. In: Freedberg I M, Eisen A Z, Wolff K, et al, eds. Fitzpatrick's Dermatology in General Medicine, Vol. 1. New York, N.Y.: McGraw-Hill; 1999: 945-1017; Pathak M A et al. J Am Acad Dermato., 1986;15:894-9; Giannotti B, Melli M C. Clin Drug Invest., 1995; 0(suppl2):57-64)) for the management of melasma and current approaches include hydroquinone, considered as the gold standard depigmenting agent and other molecules such as azelaic acid, tretinoin, alpha and beta hydroxy acids, and topical corticosteroids used as monotherapy or in various combinations (Giannotti B, Melli M C. Clin Drug Invest., 1995; 0(suppl2):57-64.; Kimbrough-Green C K, Griffiths C E M, Finkel L J et al. Arch Dermatol., 1994; 130:727-33; Gano S E, Garcia R L. Cutis., 1979; 23:239-41; Kang W H, Hcun S C, Lee S. J Dermatol., 1998; 25:87-596; Katsambas A, Antoniou C H. J Eur Acad Dermatol Venereol., 1995; 4:217-23; Kligman A M, Willis I. Arch Dermatol., 1975; 111:40-8.)
Recently, a stable fixed combination cream containing fluocinolone acetonide (FA), hydroquinone (HQ), and tretinoin (RA) was developed. Several studies have been performed, comparing this fixed combination to its three corresponding dyads of active ingredient (FA+HQ), (FA+RA), (HQ+RA). These studies demonstrated better efficacy of the triple combination (FA+HQ+RA) over each dyad, after a 8-week treatment (Taylor S, Torok H, Jones T, et al. Efficacy and safety of a new triple combination agent for the treatment of facial melasma. Cutis 2003; 72:67-72).
However, melasma being a relapsing disease, there is a real need to address how to maintain efficacy achieved after acute treatment. Five hundred and sixty nine subjects previously treated in the above mentioned studies have been included in a 12-month extension trial to evaluate the safety of the trio fixed combination (Torok H, et al. J Drugs Dermatol., 2005 Sep-Oct; 4(5):592-7). The result shown that the triple combination cream applied once daily over a long-term period is safe and tolerable. But skin atrophy is a primary concern with the long-term use of topical corticosteroids. However, in the extension study mentioned only two cases of skin atrophy were reported. Both cases of skin atrophy were mild in nature and did not lead to discontinuation in the study. However, skin atrophy remains a frequent objection of clinicians to the long-term use of topical medications containing corticosteroids. For this reason, it is necessary to determine a maintenance therapy use of triple combination cream with such a good efficacy, good tolerance without side effects. This new regimen can also be more attractive to patients who no longer apply the product every day throughout the period of treatment.
It is stated that in addition to efficacy, the triple combination cream fulfills important requirements of a maintenance therapy which are efficacy with hyperpigmentation improvement, safety with a good tolerability.